Diabetes reversed in mice

For the first time ever, University of B.C. scientists have used human embryonic stem cell transplants to reverse Type 1 diabetes in mice, giving hope to about 300 million people around the world who have the chronic disease.

A 13-member team, whose work is published in the journal Diabetes, shows that after transplantation, the stem cells matured into insulin secreting, pancreatic betacells.

The cells automatically sensed blood sugar levels to release the right amount of insulin and a few dozen diabetic mice were gradually weaned off insulin given to them over a period of months. Insulin is produced by betacell to help the body absorb sugar and use it for energy.

“Essentially, the mice were cured of their diabetes by placing the body back in charge of regulated insulin production as it is in healthy, non-diabetics,” said lead author Timothy Kieffer.

“It took about four to five months for the [stem] cells to become functional in our experiments and the mice were able to maintain good blood glucose levels even when fed a high-glucose diet,” said Kieffer, a UBC professor in the department of cellular and physiological sciences.

Type 1 diabetes – otherwise known as juvenile diabetes – is an autoimmune disease in which a patient’s immune system kills off insulin-producing cells in the pancreas. About 10 per cent of diabetics are Type 1 and typically, they must inject themselves with insulin or use pumps to control their blood glucose levels.

While pancreatic islet cell trans-plantation – pioneered at the University of Alberta several years ago – has been shown to be an effective way of reducing dependence on insulin injections, the treatment is costly and cumbersome as it requires donor cells from cadavers, which are always in short supply. As well, islet cell trans-plant patients must forever take anti-rejection drugs that can cause organ damage.

In the study methodology, mice were anesthetized and then injected with millions of cells derived from stem cells which were placed under the left kidney area.

Although the research showed that stem cells may one day provide a cure for diabetes, it also revealed hurdles to overcome before agencies like the Food and Drug Administration in the United States or Health Canada can approve the therapy.

For example, some mice developed bone or cartilage in areas where the cells were inserted, an unacceptable side-effect that future experiments must resolve.

Another obstacle is figuring out how to make the therapy work for humans so they don’t reject the cells. Mice used in the study were bred to be immuno-compromised so they wouldn’t reject the human cells as foreign invaders. Continuing studies underway at UBC, in many more mice, will determine the feasibility of a method to encapsulate stem cells in a membrane that won’t be recognized as a foreign body.

Kieffer said he’s extremely encouraged by the fact the mice were not only weaned off insulin, but they also lived well and long, despite their deficient immune systems. Still, research must continue to investigate ways to fine tune the approach so the cells don’t evolve into something other than a treatment for diabetes. In the early stages of the experiment, some mice developed fluid-filled cysts, a problem that was rectified in the laboratory.

“The fact that we [also] saw cartilage-like cells means that we failed to restrict for only desirable cells and that proves the potential risks of this approach. We need to ensure that we’re getting only what we want [insulin-producing cells] and that may be done by improving the cultivation and the recipe or by purifying the cells,” Kieffer said.

The work was funded by at least $500,000 in grants from the Canadian Institutes of Health Research, the Stem Cell Network of Canada, Stem Cell Technologies of Vancouver, the Juvenile Diabetes Research Foundation and the Michael Smith Foundation for Health Research. About half the research team was comprised of scientists from BetaLogics Venture, a research and development arm of Janssen Pharmaceuticals.